The utility of ADC measurement techniques for differentiation of low- and high-grade clear cell RCC

Purpose: To evaluate the diffusion properties of clear cell renal cell carcinoma (ccRCC) on magnetic resonance imaging (MRI) concerning their Fuhrman nuclear grades and sizes, and to compare the diagnostic performance of two ROI placement techniques for apparent diffusion coefficient (ADC) measurement (entire mass vs. only the darkest region of the mass). Material and methods: Fifty-one ccRCC were enrolled in the study and grouped into low-grade ccRCC (Fuhrman grade 1 and 2, n = 37) and high-grade ccRCC (Fuhrman grade 3 and 4, n = 14). Selective ADC (Sel-ADC) measurement was performed by placing a circular ROI that included the darkest region of the tumour on ADC map images. Extensive ADC (Ext-ADC) measurement was performed by drawing an ROI that covered the entire tumour. Results: The Sel-ADC value was lower in high-grade ccRCC (p = 0.019), whereas the Ext-ADC value did not show a statistically significant difference (p = 0.42). Sel-ADC value of a ≤ 1.405 mm2/s has a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy value of 78.6, 72.2, 73.87, 77.13, and 75.4, respectively, to differentiate high-grade from low-grade ccRCC. The size and Fuhrman grade of the ccRCC were inversely correlated with the Sel-ADC value; however, the correlations were weak (r = -0.322, p = 0.021 and r = -0.376, p = 0.006, respectively). There was no difference between ADC values of small (≤ 4 cm) and large (> 4 cm) ccRCCs. Conclusions: The ADC value of the darkest region in solid part of the ccRCC may play a role in predicting the nuclear grade of ccRCC

Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p < 0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p < 0.01; r=0.236, p < 0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies

Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review

Copyright © 2021, The Author(s) Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. Methods: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. Results: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. Conclusion: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.This study is funded by the National Institute for Health Research (NIHR) Doctoral Research Fellowship Grant (DRF-2015-08-023). JMB is partially funded by the NIHR Bristol Biomedical Research Centre and the MRC ConDUCT-II Hub for Trials Methodology Research. PRW was funded by the MRC North West Hub for Trials Methodology Research (Grant ref: MR/K025635/01).info:eu-repo/semantics/publishedVersio

Lipoic acid plays a role in scleroderma: insights obtained from scleroderma dermal fibroblasts

Abstract Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote type I collagen (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as cofactors and antioxidants and are produced by lipoic acid synthetase (LIAS). Our goals in this study were to examine whether LA and LIAS were deficient in SSc patients and to determine the effect of DHLA on the phenotype of SSc dermal fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was included as a comparison. Methods Dermal fibroblasts were isolated from healthy subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase (MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor 1 (PAI-1) and LIAS were measured by enzyme-linked immunosorbent assay. The expression of Col I was measured by immunofluorescence, hydroxyproline assay and quantitative PCR. PDGFR phosphorylation and α-smooth muscle actin (αSMA) were measured by Western blotting. Student’s t-tests were performed for statistical analysis, and P-values less than 0.05 with two-tailed analysis were considered statistically significant. Results The expression of LA and LIAS in SSc dermal fibroblasts was lower than normal fibroblasts; however, LIAS was significantly higher in SSc plasma and appeared to be released from monocytes. DHLA lowered cellular oxidative stress and decreased PDGFR phosphorylation, Col I, PAI-1 and αSMA expression in SSc dermal fibroblasts. It also restored the activities of phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of MMP-1 and MMP-3, and DHLA increased them. In contrast, TIMP-1 levels were higher in SSc, but DHLA had a minimal effect. Both DHLA and NAC increased MMP-1 activity when SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than NAC in most cases. Conclusions DHLA acts not only as an antioxidant but also as an antifibrotic because it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC, LA, or DHLA, could be beneficial for patients with SSc.http://deepblue.lib.umich.edu/bitstream/2027.42/112060/1/13075_2014_Article_411.pd

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries